Lecithin cholesterol acyltransferase, LCAT, is an enzyme that helps convert low-density lipoprotein cholesterol, LDL, the bad form of cholesterol, into high-density lipoprotein cholesterol, HDL, the good form of cholesterol. Some people have a deficiency of this enzyme, which causes them to have low HDL levels. LCAT deficiency also leads to production of an abnormal lipoprotein molecule, the structural backbone of the cholesterol molecule. Experts are divided on the health effects of lecithin cholesterol acyltransferase deficiency.
Supplementation
Supplementation may be a viable means of restoring deficient levels of lecithin cholesterol acyltransferase, according to a study on laboratory animals conducted at the Pulmonary and Vascular Medicine Branch of the National Heart, Lung, and Blood Institute, National Institutes of Health. In the study, scientists gave human lecithin cholesterol acyltransferase enzyme to enzyme-deficient mice and noted an increase in HDL levels and lower levels of very low density lipoprotein, VLDL, a bad form of cholesterol. Intravenous delivery of the enzyme, injections into the muscle and injections under the skin all produced nearly identical results. The study was published in the October 2010 issue of the "Journal of Pharmacology and Experimental Therapeutics."
Atherosclerosis
Lecithin cholesterol acyltransferase enzyme deficiency may be associated with increased risk of atherosclerosis, according to a study published in the April 2009 issue of the journal "Current Opinion in Endocrinology, Diabetes and Obesity." The review of previously published research found that the enzyme's ability to lower levels of apolipoprotein B -- the protein portion of LDL cholesterol -- could be at the heart of its cardiovascular protective activity. Patients with low levels of lecithin cholesterol acyltransferase have been found to have a modestly elevated incidence of atherosclerosis. Further human studies are needed to confirm the link between lecithin cholesterol acyltransferase and cardiovascular disease.
Cholesterol Recycling
Lecithin cholesterol acyltransferase deficiency may not be a significant factor in cardiovascular risk, according to researchers at the Center E. Grossi Paoletti, Department of Pharmacological Sciences, Università degli Studi di Milano, Italy. Aside from its role in HDL production, LCAT is believed to play a part in a process known as reverse cholesterol transport, whereby cholesterol is taken out of the cells and brought back to the liver, where it is recycled into new cholesterol molecules or turned into bile. However, when scientists gave LCAT-deficient mice extra doses of the enzyme, they did not show higher rates of reverse cholesterol transport. In fact, the enzyme-deficient mice used an alternate method of reverse cholesterol transport through white blood cells called macrophages. Researchers concluded that their results suggest that LCAT supplementation may not be an effective preventive strategy for reducing cardiovascular disease risk. The study was published in the February 2010 issue of the journal "Trends in Cardiovascular Medicine."
HDL Levels
Researchers at the National Institutes of Health found significant potential for LCAT supplementation to reduce cardiovascular disease risk, in a study conducted on laboratory animals. In the study, four days of supplementation resulted in a 22-fold increase in LCAT enxyme activity, which doubled the levels of HDL cholesterol. The production of apolipoprotein A1, the major protein component of HDL cholesterol, nearly doubled, with no change in apolipoprotein A1 levels, indicating that all of the newly formed protein was being used in the production of HDL cholesterol. Conversely, LCAT supplementation resulted in a 37 percent reduction in apolipoprotein B levels. The researchers concluded that LCAT shows promise as a potential target for drug development. The study was published in the April 2009 issue of the journal "Metabolism."
References
- "Journal of Pharmacology and Experimental Therapeutics"; Effect of Recombinant Human Lecithin Cholesterol Acyltransferase Infusion on Lipoprotein Metabolism in Mice; X. Rousset; October 2010
- "Current Opinion in Endocrinology, Diabetes and Obesity"; Lecithin: Cholesterol Acyltransferase--from Biochemistry to Role in Cardiovascular Disease; S. Rousset, et al.; April 2006
- "Trends in Cardiovascular Medicine"; Lecithin:cholesterol Acyltransferase, High-density Lipoproteins, and Atheroprotection in Humans; L. Calabresi, et al.; February 2010
- "Metabolism"; Adenoviral Expression of Human Lecithin-cholesterol Acyltransferase in Nonhuman Primates Leads to an Antiatherogenic Lipoprotein Phenotype by Increasing High-density Lipoprotein and Lowering Low-density Lipoprotein; M. Amar, et al.; April 2009
